In the olfactory bulb, a single synapse separates afferent sensory input and the principal neurons that project to higher cortical areas. Nevertheless, the vast majority of cells and connections in this structure are devoted to two distinct inhibitory circuits: one located superficially in the glomerular layer and one involving granule cells in infraglomerular layers. Soon after they were initially described, it was suggested that these inhibitory circuits might provide center-surround inhibition in an analogous fashion to other primary sensory areas. Nevertheless, the manner in which these circuits are activated by olfactory stimuli in vivo has yet to be demonstrated, and their importance in shaping olfactory bulb output remains controversial. In this proposal, the spread of inhibition laterally from the sites of olfactory receptor neuron input through the glomerular layer will be directly visualized t determine how lateral inhibition at this level might contribute to olfactory information processing In addition, the postsynaptic effect of inhibition arising from both lateral circuits will be assesed in identified olfactory bulb output neurons. These experiments will provide crucial insights into the role of lateral inhibitory circuits in vivo, and, by determining the differential effects of thse circuits on the excitability of different classes of output neurons, a better understanding of parallel pathways projecting to higher brain structures. PUBLIC HEALTH RELEVANCE: The representation of an animal's sensory environment in the brain comes about as a result of specific patterns of connectivity between neurons in sensory areas. To better understand how the olfactory system, and, more generally, all sensory systems, process sensory information, this proposal aims to describe the spatial spread of activity in inhibitory circuits and their impact on output neuron behavior in the olfactory bulb when the live animal is presented with odors. This course of study will provide new insights into the ways that information about odors are transformed by local circuits in the olfactory bulb so that we may better understand how the brain processes sensory signals generated in the animal's periphery and better address sensory deficits caused by injury and disease with new therapeutic approaches.